Authors: Murchison, Charles F. | Kennedy, Richard E. | McConathy, Jonathan E. | Roberson, Erik D.
Article Type: Research Article
Abstract: Background: African Americans are at increased risk for Alzheimer’s disease (AD) but barriers to optimal clinical care are unclear. Objective: To comprehensively evaluate potential racial differences in the diagnosis and treatment of AD in an academic medical center. Methods: We used the clinical informatics tool, i2b2, to analyze all patient encounters for AD or mild cognitive impairment (MCI) in the University of Alabama at Birmingham Health System over a three-year period, examining neuroimaging rates and dementia-related medication use by race and clinic site using ratio tests on contingency tables of stratified patient counts. Results: Enterprise-wide, African Americans were not underrepresented …among outpatients seen for AD/MCI. However, there were differences in the clinic setting where visits occurred, with African Americans overrepresented in Geriatrics and primary care clinics and underrepresented in Memory Disorders specialty clinics. There were no racial differences in the rates at which any clinic ordered PET neuroimaging tests or dementia-related medications. However, unsurprisingly, specialty clinics ordered both PET neuroimaging and dementia-related medications at a higher rate than primary care clinics, and overall across the medical enterprise, African Americans were statistically less likely to have PET neuroimaging or dementia-related medications ordered. Conclusion: African Americans with AD/MCI were not underrepresented at this academic medical center but were somewhat less likely to have PET neuroimaging or to be on dementia-related medications, potentially in part from underrepresentation in the specialty clinics where these orders are more likely. The reasons for this underrepresentation in specialty clinics are likely multifactorial and important to better understand. Show more
Keywords: African Americans, Alzheimer’s disease, cognition, dementia, geriatrics, mild cognitive impairment, neuroimaging, racial factors, referral and consultation
DOI: 10.3233/JAD-200796
Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 543-557, 2021
Authors: Murchison, Charles F. | Jaeger, Byron C. | Szychowski, Jeff M. | Cutter, Gary R. | Roberson, Erik D. | Kennedy, Richard E.
Article Type: Research Article
Abstract: Background: Accurate longitudinal modelling of cognitive decline is a major goal of Alzheimer’s disease and related dementia (ADRD) research. However, the impact of subject-specific effects is not well characterized and may have implications for data generation and prediction. Objective: This study seeks to address the impact of subject-specific effects, which are a less well-characterized aspect of ADRD cognitive decline, as measured by the Alzheimer’s Disease Assessment Scale’s Cognitive Subscale (ADAS-Cog). Methods: Prediction errors and biases for the ADAS-Cog subscale were evaluated when using only population-level effects, robust imputation of subject-specific effects using model covariances, and directly known individual-level effects fit …during modelling as a natural control. Evaluated models included pre-specified parameterizations for clinical trial simulation, analogous mixed-effects regression models parameterized directly, and random forest ensemble models. Assessment used a meta-database of Alzheimer’s disease studies with validation in simulated synthetic cohorts. Results: All models observed increases in variance under imputation leading to increased prediction error. Bias decreased with imputation except under the pre-specified parameterization, which increased in the meta-database, but was attenuated under simulation. Known fitted subject effects gave the best prediction results. Conclusion: Subject-specific effects were found to have a profound impact on predicting ADAS-Cog. Reductions in bias suggest imputing random effects assists in calculating results on average, as when simulating clinical trials. However, reduction in error emphasizes population-level effects when attempting to predict outcomes for individuals. Forecasting future observations greatly benefits from using known subject-specific effects. Show more
Keywords: Alzheimer’s disease, cognitive dysfunction, forecasting, mental status and dementia tests, statistical models
DOI: 10.3233/JAD-215553
Citation: Journal of Alzheimer's Disease, vol. 87, no. 1, pp. 489-501, 2022
Authors: Shinto, Lynne | Lahna, David | Murchison, Charles F. | Dodge, Hiroko | Hagen, Kirsten | David, Jason | Kaye, Jeffrey | Quinn, Joseph F. | Wall, Rachel | Silbert, Lisa C.
Article Type: Research Article
Abstract: Background: Cerebrovascular disease is a common cause of dementia in older adults, and potentially preventable with early intervention. Oxylipins are produced from the oxidation of long-chain polyunsaturated fatty acids (PUFA) possessing potent vascular effects. Oxylipins generated from the cytochrome P450 pathway are enzymatically converted to diols by soluble epoxide hydrolase (sEH); sEH products have been associated with small vessel ischemic disease. Little is known about oxylipins’ impact on markers of dementia risk. Objective: An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition. Methods: Thirty-seven non-demented participants with controlled hypertension (mean age 65.6 years) …were enrolled in a dementia prevention study investigating fish oil and lipoic acid on preserving cognitive function. Baseline associations between plasma oxylipins, white matter hyperintensity (WMH), and Trails-B were examined using linear regression. P450-derived diol/epoxide ratio was an indirect measure of sEH activity. Results: Omega-6 derived 9-HODE was associated with increased WMH (p = 0.017) and reduced grey matter volume (p = 0.02). Omega-6 P450-derived diol/epoxide ratio 9,10-DiHOME/9,10-EpOME was associated with increased WMH (p = 0.035) and poorer performance on Trails-B (p = 0.05); ratio14,15-DHET/14,15-EET was associated with increased WMH (p = 0.045). Omega-3 P450-derived diol/epoxide ratio 19,20-DiHDPE/19,20-EpDPE was associated with increased WMH (p = 0.04) and poorer performance on Trails-B (p = 0.04). Arachidonic acid was associated with better performance on Trails-B (p = 0.012); Omega-3 derived 16,17-EpDPE was associated with decreased WMH (p = 0.005). Conclusions: With the exception of arachidonic acid, it was specific oxylipin products, not their parent PUFAs, that were associated with unfavorable and favorable MRI and cognitive markers of dementia risk. Show more
Keywords: Alzheimer’s disease, cross-sectional studies, fatty acids, humans, oxylipins, vascular dementia
DOI: 10.3233/JAD-191197
Citation: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 65-77, 2020
Authors: Raman, Fabio | Grandhi, Sameera | Murchison, Charles F. | Kennedy, Richard E. | Landau, Susan | Roberson, Erik D. | McConathy, Jonathan | Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: Background: Tools for efficient evaluation of amyloid- and tau-PET images are needed in both clinical and research settings. Objective: This study was designed to validate a semi-automated image analysis methodology, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Methods: 127 amyloid-PET and 55 tau-PET studies with volumetric MRIs were obtained from ADNI. The BLAzER methodology utilizes segmentation of MR images by FS or NR, then visualizes and quantifies regional brain PET …data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and to detect segmentation errors. Results: BLAzER analysis required ∼5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p < 0.001) and regional tau-PET SUVRs across all Braak staging regions (r > 0.97, p < 0.001) with high inter-operator reproducibility (ICC > 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS versus NR segmentation with BLAzER, global SUVRs were strongly correlated for amyloid-PET (r = 0.9841, p < 0.001), but were systematically higher (4% on average) with NR, likely due to more inclusion of white matter with NR-defined regions. Conclusions: BLAzER provides an efficient methodology for regional brain PET quantification. FDA-cleared components and visualization of registration reduce barriers between research and clinical applications. Show more
Keywords: [18F]AV-45, [18F]AV-1451, amyloid-β, brain segmentation, neuroimaging, positron emission tomography, tau
DOI: 10.3233/JAD-190329
Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1241-1257, 2019